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Publication : Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2.

First Author  Manning BD Year  2005
Journal  Genes Dev Volume  19
Issue  15 Pages  1773-8
PubMed ID  16027169 Mgi Jnum  J:100095
Mgi Id  MGI:3586939 Doi  10.1101/gad.1314605
Citation  Manning BD, et al. (2005) Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2. Genes Dev 19(15):1773-8
abstractText  The PTEN and TSC2 tumor suppressors inhibit mammalian target of rapamycin (mTOR) signaling and are defective in distinct hamartoma syndromes. Using mouse genetics, we find that Pten and Tsc2 act synergistically to suppress the severity of a subset of tumors specific to loss of each of these genes. Interestingly, we find that the slow-growing tumors specific to Tsc2+/- mice exhibit defects in signaling downstream of Akt. However, Pten haploinsufficiency restores Akt signaling in these tumors and dramatically enhances their severity. This study demonstrates that attenuation of the PI3K-Akt pathway in tumors lacking TSC2 contributes to their benign nature.
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